2,4-di-unsaturated aliphatic amines

ABSTRACT

1. A COMPOUND SELECTED FROM THOSE OF THE FORMULA (A):   R4-C(-R3)(-Z)-C(-R14)(-Z&#39;&#39;)-(CH2)N-CH2-CH(-R2)-CH2-   C(-R13)=C(-R12)-C(-R1)=CH-CH2-N(-R8)-R9   R4-C(-R3)=C(-R14)-(CH2)N-CH2-CH(-R2)-CH2-C(-R13)=C(-R12)-   C(-R1)=CH-CH2-N(-R8)-R9   Z IS BROMO, CHLORO, FLUORO, OR THE GROUP-OR IN WHICH R IS HYDROGEN, ACETOXY, OR LOWER ALKYL; Z&#39;&#39; IS HYDROGEN BROMO, CHLORO OR FLUORO; N IS ZERO OR THE POSITIVE INTEGER ONE; EACH OF R1, E2, R3 AND R4 IS LOWER ALKYL; EACH OF R12, AND R13 AND R14 IS HYDROGEN OR LOWER ALKYL; AND EACH OF R8 AND R9 IS HYDROGEN, LOWER ALKYL, OR LOWER ALKENYL.

United States Patent 3,839,452 2,4-DI-UNSATURATED ALIPHATIC AMINES Clive A. Henrick and John B. Siddall, Palo Alto, Calif., assigmors to Zoecon Corporation, Palo Alto, Calif. No Drawing. Continuation-impart of application Ser. No. 187,897, Oct. 8, 1971, now Patent No. 3,729,486, which is a continuation-in-part of applications Ser. No. 111,650, Feb. 1, 1971, now abandoned, Ser. No. 111,702, Feb. 1, 1971, Ser. No. 111,765, Feb. 1, 1971, Ser. No. 111,766, Feb. 1, 1971, now abandoned, Ser. No. 111,770, Feb. 1, 1971, now abandoned, and Ser. No. 115,725, Feb. 16, 1971, now Patent No. 3,706,733. This application Jan. 12, 1972, Ser. No. 217,297

Int. Cl. C07c 87/26 U.S. Cl. 260-583 H 19 Claims ABSTRACT OF THE DISCLOSURE Aliphatic hydrocarbon tri-olefinic and aliphatic substituted di-olefinic amines, intermediates therefor, syn theses thereof, and the control of insects.

This is a continuation-in-part of application Ser. No. 187,897, filed Oct. 8, 1971 now US. Pat. 3,729,486 which is a continuation-in-part of applications, Ser. No. 111,650, filed Feb. 1, 1971 now abandoned, Ser. No. 111,702, filed Feb. 1, 1971, Ser. No. 111,765, filed Feb. 1, 1971, Ser. No. 111,766, filed Feb. 1, 1971 now abandoned, Ser. No. 111,770, filed Feb. 1, 1971, now aban cloned, and Ser. No. 115,725, filed Feb. 16, 1971 now US. Pat. 3,706,733, the entire disclosures of which are incorporated by reference.

This invention relates to novel aliphatic di-olefinic compounds, aliphatic tri-olefinic compounds, intermediates therefor, syntheses thereof, and the control of insects. More particularly the novel di-olefinic compounds of the present invention are represented by the following formula:

Z is bromo. chloro, fluoro or the group -OR in which R is hydrogen, carboxylic acyl, lower alkyl, cycloalkyl, aralkyl or aryl;

Z' is hydrogen, bromo, chloro or fluoro;

each of m and n is zero or the positive integer one, two

or three;

each of R and R is lower alkyl;

R is alkyl;

each of R R R is hydrogen or lower alkyl;

and

each of R R R and R is hydrogen or loWer alkyl; hydroxyalkyl, alkoxyalkyl, aryl, or aralkyl, or when taken together with the nitrogen atom to which they are attached, pyrrolidino, morpholino, piperazino or 4- alkylpiperazino.

The compounds of formula A are useful for the control of insects. The utility of these compounds as insect control agents is believed to be attributable to their juvenile hormone activity. They are preferably applied to the immature insect, namelyduring the embryo, larvae or pupae stage in view of their effect on metamorphosis and otherwise cause abnormal development leading to death or inability to reproduce. These compounds are effective 3,839,452 Patented Oct. 1, 1974 control agents for Hemipteran, such as Lygaeidae, Miridae and Pyrrhocoridae; Lepidopteran, such as Pyralidae, Noctuidae and Gelechiidae; Coleopteran, such as Tenebrionidae, Crysomelidae and Dermestidae; Dipteran, such as mosquitos, flies; Homopteran, such as aphids, and other insects. The compounds can be applied at low dosage levels of the order of 0.001 ,ug. to 25.0 g. per insect. Suitable carrier substances include liquid or solid carriers, such as water, acetone, xylene, mineral or vegetable oils, talc, vermiculite, natural and synthetic resins and silica. Treatment of insects in accordance with the present invention is accomplished by spraying, dusting or exposing the insects to the vapor of the compounds of formula A. Generally, a concentration of less than 25% of the active compound is employed. The formulations can include insect attractants, emulsifying agents or wetting agents to assist in the application and effectiveness of the active ingredient. In the application of the compounds, there is generally employed a mixture of C2,3 trans and CIS 1somers.

In the description hereinafter, each of RR R R R R Z, Z, m and n is as defined hereinabove, unless otherwise specified.

In another embodiment of the present invention, there is provided compounds of the following formula B which are useful for the control of insects in the same manner as the diolefinic compounds of formula A and which also serve as precursors for the preparation of the compounds of formula A.

a u R1: 12

R (B) The compounds of formula A and B can be prepared according to the syntheses described below and the examples provided hereinafter.

In accordance with the present invention, amines of formula A and B can be prepared by the reaction of an allylic halide of formula A or B with an amine of formula C (X is bromo, chloro or iodo).

The reaction is usually carried out in an organic solvent inert to the reaction such as a hydrocarbon solvent and generally at a temperature of about room temperature or above. Usually equimolar amounts of an allylic halide of formula A or B and an amine of formula C is employed or an excess of an amine of formula C.

Preparation of allylic halides of formula A and B is fully described in application Ser. No. 187,897, filed Oct. 8, 1971 which is incorporated by reference. Briefly stated, halides of formula A and B are prepared by reduction of an il-unsaturated ester or acid to the respective allylic alcohol which is, in turn, halogenated to prepare the allylic alcohol precursor of formula A or B'. As described in Ser. No. 187,897, for example, the a,,B-unsaturated ester or acid precursor can be prepared, for example, by the reaction of a carbonyl of formula I or I with a carbanion of formula II (R is lower alkyl and R is lower alkoxy):

The compounds of formula A wherein Z is hydrogen and Z is halo can be prepared also by treating a compound of formula B with hydrogen halide in carbon tetrachloride or other halogenated hydrocarbon solvents of low dielectric constant. The compounds of formula A wherein Z is halo can be prepared also by treating a compound of formula B with bromine, chlorine or fluorine in a halogenated hydrocarbon solvent.

The compounds of formula A wherein Z is hydrogen and Z is the group OR in which R is hydrogen can be prepared also by the addition of water to the terminal olefinic bond of a compound of formula B using a mercuric salt followed by reduction of the oxy-mercurial intermediate in situ. Suitable mercuric salts include mercuric acetate, mercuric nitrite, mercuric trifluoroacetate, mercuric acylates and mercuric halides. Suitable reducing agents include the borohydride, hydrazine and sodium amalgam. See Brown and Rei, J. Am. Chem. Soc. 91, 5456 (1969); Brown et al., J. Am. Chem. Soc. 89, 1522 and 1524 (1968); and Wakabayashi, J. Med. Chem. 12, 191 (January, 1969). By conducting the reaction in the presence of an alcohol (ROH) such as methanol, ethanol, isopropyl alcohol, benzyl alcohol, cyclopentanol, and the like, the corresponding ether is prepared. The compounds of formula A wherein Z is OR in which R is carboxylic acyl and Z is hydrogen can be prepared from a compound of formula A wherein Z is OH and Z is hydrogen by reaction with a carboxylic acid chloride or bromide or carboxylic acid anhydride in pyridine or by treatment with a carboxylic acid anhydride in the presence of sodium acetate. The reaction is generally conducted at about room temperature to reflux temperature for about one to forty-eight hours, shorter reaction time being favored by temperatures above room temperature.

The term cycloalkyl, as used herein, refers to a cyclic alkyl group of four to eight carbon atoms. The term aralkyl refers to a monovalent hydrocarbon group in which an aryl group is substituted for a hydrogen atom of an alkyl group, such as benzyl, xylyl, mesityl, phenylethyl, methylbenzyl, naphthylmethyl and naphthylethyl containing up to twelve carbon atoms. The term aryl, as used herein, refers to an aromatic group of up to twelve carbon atoms. Typical aromatic groups include phenyl, naphthyl, lower alkylphenyl such as methylphenyl, ethylphenyl, t-butylphenyl and isopropylphenyl, lower alkyl thiophenyl such as methylthiophenyl, ethylthiophenyl and isopropylthiophenyl, lower alkoxyphenyl such as methoxyphenyl and ethoxyphenyl, halophenyl such as chlorophenyl, bromophenyl, iodophenyl and fiuorophenyl, nitrophenyl, methylenedioxyphenyl, and lower alkenylphenyl such as vinylphenyl and allylphenyl. In the case of substituted phenyl, the substituent such as lower alkyl, lower alkylthio, lower alkoxy, halo, nitro, lower alkenyl, lower alkoxycarbonyl and cyano can be in one or more positions of the phenyl ring, usually in the para position.

The term hydroxyalkyl, as used herein, refers to an alkyl group substituted with one hydroxy group, e.g. hy droxymethyl, p-hydroxyethyl and 4-hydroxypentyl. The term alkoxyalkyl, as used herein, refers to an alkyl group substituted with one alkoxy group, e.g. methoxymethyl, Z-methoxyethyl, 4-ethoxybutyl, n-propoxyethyl and t-butoxyethyl. The term alkenyl, as used herein, refers to an ethylenically unsaturated hydrocarbon group, branched or straight chain, having a chain length of two to twelve carbon atoms, e.g. allyl, vinyl, 3-butenyl, 2- hexenyl and i-propenyl. Whenever any of the foregoing terms are modified by the word lower, the chain length of the group is not more than six carbon atoms with the exception of lower alkoxyalkyl in which event a total chain length of twelve carbon atoms is the maximum.

The term carboxylic acyl, as used herein, refers to the acyl group of a carboxylic acid, anhydride or halide. The acyl group is determined by the particular carboxylic acid halide or carboxylic acid anhydride employed in the esterification. Although no upper limitation need be placed on the number of carbon atoms contained in the acyl group within the scope of the present invention, generally it contains from one to eighteen carbon atoms. Typical esters of the present invention include formate, acetate, propionate, enanthate, benzoate, trimethylacetate, trichloroacetate, trifluoroacetate, t-butylacetate, phenoxyacetate, cyclopentylpropionate, aminoacetate, B-chloropropionate, adamantoate, octadec-9-enoate, dichloroacetate, butyrate, pentanoate, hexanoate, phenylacetate, pmethylbenzoate, B-phenylpropionate, 3,4-dimethylbenzoate, p-isopropylbenzoate, cyclohexylacetate, stearate, methacrylate, p-chloromethylbenzoate, p-methoxybenzoate and p-nitrobenzoate.

The term alkyl refers to a branched or straight chain, saturated aliphatic hydrocarbon of one to twelve carbon atoms. The term lower alkyl refers to an alkyl group having a chain length of one to six carbon atoms.

In addition to the compounds of the present invention having activity useful for the control of insects, the compounds of formula A and B are useful wetting and cleansing agents per se for textiles and as intermediates therefor using the method of U.S. Pat. 2,169,976.

The presence of an olefinic bond at position C-2 and C-4 of the compounds of formula A give rise to four isomers, each of which is embraced by the present invention. The presence of three olefinic bonds in compounds of formula B give rise to eight isomers, each of which is embraced by the present invention.

As mentioned above, a mixture of isomers is suitably employed for the control of insects such as a mixture containing the trans (2), trans (4) isomer and the cis (2), trans (4) isomer. The conditions of the synthesis described herein and the reactants can be selected so as to favor formation of one isomer such as the all trans isomer over the formation of other isomers. The selection of appropriate conditions and reactants to favor formation of one isomer over another will be apparent to those of ordinary skill in the art giving due consideration to the specific examples hereinafter. See also Pattenden and Weedon, supra and Corey et al., supra. In the specific examples hereinafter, when isomerism is not specified, it is understood to include a mixture of isomers which, if desired, can be separated using known separation methods. Hereafter, when only one designation of configuration is given, the designation refers to position C-2,3 and configuration is taken to be trans at position C-4,5 when not otherwise specified. The use of trans/cis and cis/ trans is with reference to position C2,3 and indicates a mixture of isomers.

The following examples are provided to illustrate the practice of the present invention. Temperature is given in degrees centigrade.

EXAMPLE 1 To a mixture of one g. of 3,7-dimethyloct-6-en-l-al 1.5 g. of phosphonate (II; R is ethyl, R is methyl, R is ethoxy, R is hydrogen) and 50 ml. of dimethylformamide, under nitrogen, is slowly added sodium ethoxide (prepared from 200 mg. of sodium and 12 ml. of ethanol).

EXAMPLE 2 The process of Example 1 is repeated using each of the aldehydes under column I as the starting material to yield the respective ester under column II 3,7-dimethylnon-6-en-1-al 3-ethyl-7-methylnon-6-en-l-al 3,7-diethylnon-6-en-1-al 4,8-dimethylnon-7-enl-al 3 ,G-dimethylhept-S-enl-al 3,6-dimethyloct--enl-al 2,G-dimethylhept-S-en-l-al.

ethyl 3,7,1 1-trimethyltrideca2,4, lO-trienoate ethyl 3,11-dimethyl-7-ethyltrideca-2,4,IO-trienoate ethyl 7,11-diethyl-3-methyltrideca-2,4,lO-trienoate ethyl 3,8, l2-trimethyltrideca-2,4, l l-trienoate ethyl 3,7,10-trimethylundeca-2,4,9trienoate ethyl 3,7,10-trimethyldodeca-2,4,9-trienoate ethyl 3,6,10-trimethylundeca-2,4,9-trienoate.

EXAMPLE 3 A mixture of 1 g. of trans/cis methyl 3,7,11-trimethyldodeca-2,4,10-trienoate, 60 ml. of methanol, 0.5 g. of potassium hydroxide and 6- ml. of water is heated at reflux for about 8 hours. The mixture is then diluted with water, neutralized and extracted with ether. The organic phase is washed with water, dried over sodium sulfate and evaporated to yield trans/cis 3,7,11-trimethyldodeca-2,4,10-trienoic acid.

Using the foregoing procedure, the other esters of Example 2 are hydrolyzed to produce the respective free acids under column III.

III

3,7 ,1 1-trimethyltrideca-2, 4,10-trienoic acid 3,1 1-dimethyl-7-ethyltrideca-2,4, 1 O-trienoic acid 7,1 1-diethyl-3-methy1trideca-2,4, IO-trienoic acid 3 ,8,12-trimethyltrideca-2,4,1 l-trienoic acid 3,7,10-trimethylundeca-Z,4,9 trienoic acid 3,7,10-trimethyldodeca-2,4,9 trienoic acid 3,6,10-trimethylundeca-2,4,9=trienoic acid.

EXAMPLE 4 One gram of thionyl chloride is added with stirring at room temperature to 0.5 g. of trans/cis 3,7,11-trimethyldodeca-2,4,10-trienoic acid and the mixture heated at about 50 for 10 minutes. Excess thionyl chloride is removed by evaporation and then t-butyl alcohol (about 2 equivalents) is added and the mixture heated at about 50 for about five minutes to yield t-butyl 3,7,l1-trimethyldodeca-2,4,10-trienoate(trans/cis) By using other alcohols in place of t-butyl alcohol in the process of this Example, such as cyclohexyl alcohol, isopropyl alcohol, benzyl alcohol, n-pentanol, n-hexanol, or n-propanol, the respective esters are prepared, i.e.,

cyclohexyl 3 ,7, l 1trimethyldodeca-2,4, 1 O trienoate isopropyl 3,7,1 1-trimethy1dodeca-2,4, IO-trienoate benzyl 3 ,7,1 1-trimethy1dodeca-2,4, 1 O-trienoate n-pentyl 3,7 ,1 1-trimethyldodeca-2,4, 10-trienoate n-hexyl 3,7,1 1-trimethyldodeca-2,4, IO-trienoate n-propyl 3,7,11-trimethyldodeca-2,4,IO-trienoate.

6 EXAMPLE 5 To a solution of 0.5 g. of trans/cis 3,7,l1-trimethyldodeca-2,4,10-trienoic acid in 15 ml. of benzene is added with stirring an equivalent amount of potassium bicarbonate. The mixture is stirred until the evolution of carbon dioxide ceases and then evaporated to yield potassium 3,7,11-trimethyldodeca-2,4,10-trienoate.

Alternatively, acid salts can be prepared by titrating the acid with an organic solution or aqueous organic solution of the desired metal.

EXAMPLE '6 One gram of 3,7,11-trimethyltrideca-2,4,10-trienoic acid in 30 ml. of benzene and one mol. of sodium hydride is stirred about two hours and then a slight excess of oxalyl chloride is added at about 0 and stirred for one hour. The product is worked up by removal of solvent in vacuo and extraction with pentane to yield 3,7,11-trimethyltrideca-2,4,lO-trienoyl chloride.

EXAMPLE 7 A. To magnesium propynylide (15 g.) in 150 ml. of ether is slowly added 0.3 moles of 3,7-dimethyloct-6-enl-al and the mixture then stirred overnight. Saturated aqueous ammonium chloride is added and the layers sep arated. The organic phase, combined with ether backwashings of aqueous phase, is washed with water, dried and solvent evaporated to yield 6,10-dimethyl-9-undecen 2-yn-4-ol which can be purified by chromatography.

B. A mixture of 18.5 g. of the alkynyl alcohol of part A, g. of triethylorthoacetate and 0.7 g. of propionic acid is refluxed under a spinning band column to remove ethanol as it is formed. After the elimination of ethanol is about complete, the crude reaction product is distilled under vacuum to yield ethyl 3,7,1l-trimethyldodeca-3,4,10- trienoate. Alternatively, the crude reaction product is purified by chromatography on silica.

C. A solution of 1.0 g. of the allenic ester of part B in 20 ml. of ethanol is treated with 4 ml. of aqueous 2N sodium hydroxide and left at room temperature for several minutes. The mixture is then poured into pentane and washed with saturated brine and separated. Evaporation of the organic phase yields ethyl 3,7,11-trimethyldodeca- 2,4,10-trienoate.

EXAMPLE 8 The process of Example 7, part A, is repeated using each of the aldehydes under column I as the starting material to yield the respective alkynyl alcohol under column IV, each of which is reacted with triethylorthoacetate using the process of Example 7, part B, to prepare the respective allenic ester under column V.

IV 6,10-dimethyl-9-dodecen-2-yn-4-ol 6-methyl-10-ethyl-9-dodecen-2-yn-4-01 6,10-diethyl-9-dodecen-2-yn-4-ol 7,1 I-dimethyl-l 0-dodecen-2-yn-4-ol 6,9-dimethyl-8-decen-2-yn-4-ol 6,9-dimethyl-8-undecen-2-yn-4-ol 5,9-dimethyl-8-decen-2-yn-4-ol.

ethyl 3,7,1 l-trimethyltrideca-3,4, l O-trienoate ethyl 3,1 1-dimethyl-7-ethyltrideca-3,4,10-trienoate ethyl 3-methyl-7,1l-diethyltrideca-3,4,10-trienoate ethyl 3,8,12-trimethyltrideca-3,4,1 l-trienoate ethyl 3,7,10-trimethylundeca-S,4,9-trienoate ethyl 3,7,10-trimethyldodeca-3,4,9-trienoate ethyl 3,6,10-trimethylundeca-3,4,9-trienoate.

Using the process of Example 7, part C, each of the allenic esters under column V is rearranged by treatment with aqueous sodium hydroxide to produce the respective a,,B-unsaturated ester.

7 EXAMPLE 9 To 126 mg. of a 57% dispersion of sodium hydride in oil is added pentane. The pentane is removed and the sodium hydride washed several times with pentane. To the washed sodium hydride is added 582 mg. of diethyl acetyl-methylphosphonate (lIA; R is ethyl, R is methyl, R is hydrogen) in ml. of tetrahydrofuran at -10 under argon. After several minutes, the solution is transferred to a solution of 425 mg. of 3,7-dimethyloct-6-enl-al in about 4 ml. of dry tetrahydrofuran under argon over a period of about minutes at room temperature. After about two hours, water is added followed by addition of ether and the layers separated. The organic layer is Washed with saturated sodium chloride, dried over sodium sulfate and evaporated under reduced pressure to yield 6,10-dimethylundeca-3,9-dien-2-one.

EXAMPLE 10 One gram of triphenylphosphineacetylmethylene and 425 mg. of 3,7-dimethylnon-6-en-l-al are dissolved in 10 ml. toluene and refluxed under nitrogen overnight. The toluene is distilled oil and the formed triphenylphosphine oxide crystallized by addition of pentane. Filtration and evaporation of the pentane gives a residue, which is further purified by preparative thin layer chromatography to yield 6,l0-dimethyldodeca-3,9-dien-2-one.

EXAMPLE 11 41 Grams of 3,7-dimethyloct-6-en-l-al and 80 g. of recrystallized (ethyl acetate) triphenylphosphineacteylmethylene [Ramirez et al., J. Org. Chem. 22, 41 (1957)] are refluxed in one liter of dry toluene for 18 hours, under nitrogen. Most of the solvent is removed in vacuo, 500 ml. pentane is added and the mixture filtered. The flask and the triphenylphosphine oxide filter cake are washed several times with pentane. The filtrate is con centrated under vacuum to yield 6,10-dimethylundeca- 3,9-dien-2-one.

EXAMPLE 12 Using the process of either of Example 9, 10 or 11, each of the aldehydes under column I is converted into the respective di-unsaturated ketone under column VI.

6,l0-dimethyldodeca-3,9-dien-2-one 6-methyl-10-ethyldodeca-3,9-dien-2-0ne 6,10-diethyldodeca-3,9-dien-2-one 7,1l-dimethyldodeca-3,10-dien-2-one 6,9-dimethyldeca-3 ,8-dien-2-one 6,9-dimethylundeca-3 ,8-dien-2-one 5 ,9-dimethyldeca-3 ,8-dien-2-one.

EXAMPLE 13 The carbanion of diethyl carbomethoxymethyl phosphonate is reacted with 6,10-dimethylundeca-3,9-dien-2- one and each of the ketones under column VI using the procedure of either Example 1 or 9 to prepare the respective methyl esters under column VII.

VII

methyl 3,7,11-trimethyldodeca-2,4,IO-trienoate methyl 3,7,1 l-trimethyltrideca-2,4,10-trienoate methyl 3,1 1-dimethyl-7-ethyltrideca-2,4,IO-trienoate methyl 3-methyl-7,1 1-diethyltrideca-2,4,lO-trienoate methyl 3 ,8, l2-trimethyltrideca-2,4,1 l-trienoate methyl 3,7,10-trimethylundeca-2,4,9-trienoate methyl 3,7,10-trimethyldodeca-2,4,9-trienoate methyl 3,6,10-trimethylundeca-2,4,9-trienoate.

EXAMPLE 14 Anhydrous hydrogen chloride is bubbled into 100 ml. of dry carbon tetrachloride at 0 until six equivalent is taken up. Five grams of trans ethyl 3,7,11-trimethyldodeca-2,4,lO-trienoate is added and the resulting mixture allowed to stand for about 48 hours at 0. The mixture is evaporated under reduced pressure to yield trans ethyl 11-chloro-3,7,l1-trimethyldodeca-2,4 dienoate which is purified by chromatography.

The above process is repeated using each of the unsaturated esters under Column II to prepare the respective. compound under Column VIII.

VIII

ethyl 1 l-chloro-3,7, l l-trimethyltrideca-2,4-dienoate, ethyl 1 l-chloro-3,1 1-dimethyl-7-ethyltrideca-2,4-dienoate, ethyl 1 1-ch1oro-7,11-diethyl-3-methyltrideca-2,4-dienoate, ethyl l2-chloro-3,8,1Z-trimethyltrideca-Z,4-dienoate, ethyl 10-chloro-3,7,10-trimethylundeca-2,4-dienoate, ethyl 10-chloro-3,7,10-trimethyldodeca-2,4-dienoate, and ethyl l0-chloro-3,6,10-trimethylundeca-2,4-dienoate.

Each of the esters under col. VII is used as the starting material in the process of this example to prepare the hydrochlorides under col. IX.

EXAMPLE 15 Each of benzyl 3,7,1l-trimethyltrideca-2,4,10-trienoate, isopropyl 3,7,11 trimethyldodeca-2,4,10-trienoate, cyclohexyl 3,7,1l-trimethyldodeca-2,4,IO-trienoate and n-hexyl 3,7,10-trimethylundeca-Z,4,9-trienoate is used as the starting material in the procedure of Example 14 to prepare the respective compound, that is benzyl 1 lchloro-3,7,11-trimethyltrideca-2,4-dienoate,

isopropyl l l-chloro-3,7,l l-trimethyldodeca-2,4-dien0ate,

cyclohexyl l l-chloro-3,7,1l-trimethyldodeca-2,4-

dienoate, and

n-hexyl 10-chloro-3,7,1 1-trimethylundeca-2,4-dienoate.

EXAMPLE 16 One gram of trans ethyl 3,7,1l-trimethyldodeca-2,4,10- trienoate is added to a solution of 6 equiv. of dry hydrogenfluoride in dry tetrahydrofuran. The mixture is allowed to stand at 0 for 45 hours and is then washed with water, dried and evaporated under reduced pressure to yield trans ethyl 11-fluoro-3,7,11-trirnethyldodeca-2,4- dienoate which can be purified by chromatography.

EXAMPLE 17 The process of Example 14 is repeated with the exception of using dry hydrogen bromide in place of hydrogen chloride to yield trans ethyl 11-bromo-3,7,11-trimethyldodeca-Z,4-dienoate.

By treating the 11-bromide with anhydrous silver fluoride in acetonitrile under reflux conditions for about six hours, there is prepared trans ethyl 11-fluoro-3,7,11- trimethyldodeca-2,4-dienoate.

EXAMPLE 18 Chlorine gas is bubbled into 200 ml. of carbon tetrachloride at 0 until six equivalent is taken up. Twenty-five grams of trans ethyl 3,7,1l-trimethyldodeca-2,4,10- trienoate is added and the mixture is then stirred and then allowed to stand at about 0 for 60 hours. The mixture is then evaporated to yield trans ethyl 10,11-dichloro-3,7,11- trimethyldodeca-2,4-dienoate which can be purified by chromatography.

EXAMPLE 19 To a mixture of g. of trans ethyl 3,7,ll-trimethyldodeca-2,4,10-trienoate in 100 ml. of fluorotrichloromethane is slowly added 1 equiv. of dry fluorine in about one hour at about -78. After stirring the mixture at this temperature for about 16 hours, the resultant mixture is evaporated and chromatographed on silica to yield trans ethyl 10,-1 1-difiuor0-3,7, 1 1-trimethyldodeca-2,4-dienoate.

By using bromine in the process of Example 18 there is prepared trans ethyl 10,11 dibrorno-3,7,1l-trimethyldodeca-2,4-dienoate.

EXAMPLE 20 To a mixture of 1.9 g. of mercuric acetate, 6 ml. of water and 20 ml. of tetrahydrofuran is added 1.49 g. of trans ethyl 3,7,1l-trimethyldodeca-2,4,10-trienoate slowly. After addition is complete, the reaction mixture is stirred for about 20 minutes. The mixture is cooled to about 0 and 6 ml. of aqueous sodium hydroxide (3 molar) is added followed by 0.49 g. of sodium borohydride in aqueous sodium hydroxide (about 3 molar). The mixture is stirred for about 30 minutes. The mixture is then decanted, concentrated, diluted With water and then extracted with ether. The ethereal extract is washed with water, dried over magnesium sulfate and the product chromatographed on silica gives ethyl 11-hydroxy-3, 7,1 1-trimethyldodeca-2,4-dienoate (trans).

The above process is repeated using each of the unsaturated esters under Column II to prepare the respective compound under Column X.

ethyl 1 1-hydroxy-3,7 ,1 1-trimethyltrideca-2,4-dienoate,

ethyl 11-hydroXy-3,1l-dimethyl-7-ethyltrideca-2,4-

dienoate,

ethyl 1 1-hydroxy-7, 1 1-diethyl-3-methyltrideca-2,4-

dienoate,

ethyl 12-hydroxy-3,8,lZ-trimethyltrideca-2,4-dienoate,

ethyl -hydroxy-3,7,10-trimethylundeca-2,4-dienoate,

ethyl 10-hydroxy-3,7,10-trimethyldodeca-2,4-dienoate,

and

ethyl 10-hydroxy-3,6,10-trimethylundeca-2,4-dienoate.

EXAMPLE 21 Each of the esters under Column VII is used as the starting material in the process of Example to prepare the respective hydroxyl under Column XI:

methyl 1 1-hydroxy3,7,11-trimethyldodeca-2,4-dienoate,

methyl 1 1-hydroxy-3,7,11-trimethyltrideca-2,4-dienoate,

methyl 11-hydroxy-3,1 1-dimethyl-7-ethyltrideca-2,4-

dienoate,

methyl 1 l-hydroxy-3-methyl-7,l l-diethyltrideca-2,4-

dienoate,

methyl 12-hydroxy-3,8,12-trimethyltrideca-2,4-dienoate,

methyl 10-hydroxy-3,7,10-trimethylundeca-2,4-dienoate,

methyl 10-hydroxy-3,7,lO-trimethyldodeca-2,4-dienoate,

and

methyl 10-hydroxy-3,6,10-trimethylundeca-2,4-dienoate.

EXAMPLE 22 Each of benzyl 3,7,11-trimethyltrideca-2,4,IO-trienoate, isopropyl 3,7,11-trimethyldodeca-2,4,l0-trienoate, cyclohexyl 3,7,11-trimethyldodeca-2,4,10-trienoate and n-hexyl 3,7,l0-trimethylundeca-2,4,9-trienoate is used as the starting material in the process of Example 20 to prepare the respective hydroxy, that is benzyl 1 1-hydroxy-3,7,11-trimethyltrideca-2,4-dienoate,

isopropyl 1 1-hydroxy-3,7,1 1-trimethyldodeca2,4-

dienoate,

cyclohexyl 1 1-hydroxy-3,7,1 1trimethyldodeca-2,4-

dienoate, and

n-hexyl 10-hydroxy-3 ,7 1 O-trimethylundeca-2,4-dienoate.

10 EXAMPLE 23 To a solution of 2 g.'of trans ethyl 3,7,11-trimethyldodeca-2,4,10-trienoate in 20 ml. of ethanol, cooled to 0 in an ice bath, is added a suspension of 2.32 g. of mercuric acetate in 50 ml. of ethanol over 15 minutes. The reaction mixture is stirred for two hours and then, with cooling, 1.22 g. of potassium hydroxide in 20 ml. of ethanol is added. Then 0.139 g. of sodium borohydride is added in small portions and stirring continued for 30 minutes. The solution is decanted, then concentrated to half volume, diluted with ml. of water and extracted with ether (3X50). The ethereal phase is Washed with Water, dried over magnesium sulfate and the crude product chromatographed on silica using hexane:ether to yield trans ethyl 11 ethoxy 3,7,11 trirnethyldodeca-2,4 dienoate.

EXAMPLE 24 A mixture of 1 g. of trans ethyl 11-hydroxy-3,7,l1- trimethyldodeca-2,4-dienoate, 10 ml. of acetic anhydride and 0.5 g. of dry sodium acetate is refluxed for about five hours. After cooling, excess anhydride is removed by vacuum and the residue extracted wtih ether. The ethereal extract is washed, dried over magnesium sulfate and evaporated to yield the corresponding acetate, trans ethyl 1 l-acetoxy-3,7,1 1-trimethyldodeca-2,4-dienoate.

EXAMPLE 25 A mixture of 2 g. of dry trans ethyl 11-hydroxy-3,7,11- trimethyldodeca-2,4dienoate, 15 ml. of acetyl chloride and 20 ml. of dry pyridine under nitrogen is heated on a steam bath for about six hours. After cooling, the mixture is concentrated under vacuum and the residue taken up in ether. The ethereal extract is washed, dried over magnesium sulfate and evaporated to yield the corresponding acetate, trans ethyl 11-acetoxy-3,7,1l-trimethyldodeca-2,4-dienoate.

The process of this example is repeated with the exception of using triethylamine in place of pyridine to yield the ll-acetate.

EXAMPLE 26 One gram of trans ethyl 11-hydroxy-3,7,1l-trimethyldodeca-2,4-dienoate in 10 ml. of diglyme is added dropwise to a slurry of 1 g. of sodium hydride in 10 ml. of diglyme under nitrogen. To this mixture is added 0.9 g. of cyclohexylchloride. The reaction mixture is stirred at about 25 for 30 minutes and then quenched in ice water. The organic phase is separated and aqueous phase reextracted with ether. The organic materials are washed with water, dried over sodium sulfate and evaporated to yield the cyclohexyl ether of trans ethyl 11-hydroxy-3,7, ll-trimethyldodeca 2,4-dienoate.

By using each of benzyl chloride and cyclopentyl chloride in the foregoing procedure, the corresponding benzyl ether and cyclopentyl ether is prepared.

EXAMPLE 27 By use of the procedure of Example 25, ethyl ll-hydroxy 3,7,11-trimethyldodeca-2,4-dienoate is converted into the corresponding ll-chloroacetate, ll-dichloroacetate and ll-tri-chloroacetate using chloroacetyl chloride, dichloroacetyl chloride and trichloroacetyl chloride, respectively.

The respective ll-trifluoroacetate, propionate, n-butanoate, n-pentanoate and n-hexanoate ester of ethyl 11- hydroxy-3,7,11-trimethyldodeca-2,4-dienoate are prepared according to the process of Example 24 using trifluoroacetic anhydride, propionic anhydride, n-butyric anhydride, n-pentanioc anhydride and n-hexanoic anhydride or according to the process of Example 25 using the corresponding acid chloride.

EXAMPLE 28 A mixture of 20 ml. of dry formic acid and 2 g. of trans ethyl 3,7,11 trimethyldodeca 2,4,10 trienoate is heated at 50 for two hours and then poured onto ice cold potassium bicarbonate solution. The reaction is worked up by extraction with ether, washing the ethereal extract, drying over magnesium sulfate and evaporation to yield the formate of trans ethyl 1l-hydroxy-3,7,1l-trimethyldodeca-2,4-dienoate.

Using the above process, the formates of formula A are prepared from the corresponding precursor of formula B having a terminal olefinic bond.

EXAMPLE 29 Fifteen grams of mercuric acetate in 50 ml. of dry ethanol is added to 12 g. of trans ethyl 3,7,11-trimethyldodeca-2,4,10-trienoate in 30 ml. of dry ethanol cooled in an ice bath. The temperature is allowed to come to room temperature by standing overnight. Then the mixture is cooled to g. of potassium hydroxide in 150 ml. of ethanol is added followed by addition of 1.0 g. of sodium borohydride in small portions. After about 30 minutes at 0, water is added and mixture left at room temperature for two hours. The mixture is filtered, filtrate concentrated and extracted with ether. The ethereal extract is washed, dried, and evaporated to yield trans ethyl 11 ethoxy 3,7,11 trimethyl-dodeca-2,4- dienoate which is purified by distillation or chromatography.

By using methanol in the foregoing process in place of ethanol, there is prepared the respective ll-methyl ether. In the same way, each of isopropanol, t-butanol, and n-propanol is added to the terminal double bond to prepare:

ethyl 11-isopropoxy-3,7,1 1-trimethyldodeca-2,4-dienoate,

ethyl 1 1-t-butoxy3-,7,1 1-trimethyldodeca-2,4-dienoate,

and

ethyl 1 l-n-propoxy-3,7 ,1 1-trimethyldodeca-2,4-dienoate.

EXAMPLE 30 'Each of the tri-unsaturated esters under col. VII is used as the starting material in the process of Example 21 or 29 to yield the respective ethoxy substituted compound under col. XII.

XII

methyl 1 1-ethoxy-3,7,1 1-trimethyldodeca-2,4-dienoate.

methyl 1l-ethoxy3,7,11-trimethyltrideca-2,4-dienoate,

methyl 11-ethoxy3,l1-dimethyl-7-ethyltrideca-2,4-

dienoate,

methyl 1 1-ethoxy-3-methyl-7,11-diethyltrideca-2,4-

dienoate,

methyl 12-ethoxy-3,8,l2-trimethyltrideca-2,4-dienoate,

methyl 10-ethoxy-3,7,10-trimethylundeca-Z,4-dienoate,

methyl 10-ethoxy-3,7,10-trimethyldodeca-2,4-dienoate,

and

methyl 10-ethoxy-3,6,lO-trimethylundeca-2,4-dienoate.

EXAMPLE 31 A mixture of 1 g. of trans methyl 1l-ethoxy-3,7,11- trimethyldodeca-2,4-dienoate, 60 ml. of methanol, 0.5 g. of potassium hydroxide and 6 ml. of water is heated at reflux for about eight hours. The mixture is then diluted with water, neutralized and extracted with ether. The organic phase is washed with water, dried over sodium sulfate and evaporated to yield trans 11-ethoxy-3,7,11- trimethyldodeca-2,4-dienoic acid.

EXAMPLE 32 Using each of the esters under Column II as the starting material in the process of either Example 22 or 29, there is prepared the respective substituted ester under Column XHI.

XIII r ethyl 11-ethoxy-3,7,11-trimethyldodeca-2,4-dienoate,

ethyl 1 1-ethoxy-3 ,7 ,1 1-trimethyltrideca-2,4-dienoate,

ethyl l1-ethoxy-3,11-dimethyl-7-ethyl trideca-2,4-

dienoate,

ethyl 11-ethoxy-7,l 1-diethyl-3-methyltrideca-2,4-

dienoate,

ethyl 12-ethoxy-3, 8,1Z-trimethyltrideca-2,4-dienoate,

ethyl 10-ethOxy-3,7,10-trimethylundeca-2,4-dienoate,

ethyl lO-ethoxy-3,7,10-trimethyldodeca-2,4-dienoate, and

ethyl l0-ethoxy-3,6,10-trimethylundeca-2,4-dienoate.

EXAMPLE 33 (A) To a mixture of 50 g. of 7-methoxy-3,7-dimethyloctan-l-al, 75 g. of diethyl 3-ethoxycarbonyl-Z-methylprop-2-enyl phosphonate (49% trans), and 500 ml. of dimethylformamide, under nitrogen, at 0, and with stirring, is slowly added 9 g. of sodium in 250 ml. of ethanol. After addition is complete, the reaction is allowed to continue one hour at room temperature. The reaction is worked up with hexane, filtered through Florisil and filtrate evaporated to yield trans( 2), trans(4) and cis(2), trans(4) ethyl 11-methoxy-3,7,1l-trirnethyldodeca-2,4-dienoate (about 60% trans, trans).

(B) A mixture of 45 g. of the ethyl ester of part A, 350 ml. of ethanol, ml. of water and 70 ml. of 50% aqueous NaOH is refluxed for 22 hours. Ethanol is then removed under reduced pressure, water added followed by extraction with ether. The aqueous phase is adjusted to about pH 8 using aqueous HCl and 31 g. of S-benzylisothiouronium hydrochloride in water is added. The thusformed salt is filtered, Washed with water, recrystallized from aqueous methanol (twice) and then treated with aqueous HCl/ether and worked up to yield ll-methoxy- 3,7,11-trimethyldodeca-2,4-dienoic acid which crystallizes on cooling.

(C) The acid (0.5 g.) of part B is methylated using diazomethane in ether, followed by chromatography on prep. TLC and distillation (short path) to prepare methyl l1 methoxy-3,7,11-trimethyldodeca-2,4-dienoate [95.2% trans(2), trans(4)]. In the same way, using diazoethane is prepared ethyl 11-methoxy-3,7,11-trimethyldodeca-2,4- dienoate [95.2% trans(2), trans(4)].

EXAMPLE 34 To 0.5 g. of the acid of Example 33 in 10 ml. of benzene, under nitrogen, is added 0.055 g. of sodium hydride. After stirring at room temperature for 15 minutes, 0.17 ml. of oxalyl chloride is added followed by stirring for 2.5 hours. Then 2 ml. of isopropanol is added. After about 3 hours, the reaction is worked up by extraction with ether, washing with sodium bicarbonate and brine, drying over calcium sulfate and isolation to yield isopropyl 11 methoxy-3,7,11-trimethyldodeca-2,4-dienoate (about 91% trans, trans).

EXAMPLE 35 To 0.5 g. of the acid of Example 33 in 10 ml. of benzene, under nitrogen is added 0.17 ml. of oxalyl chloride which is stirred for about 45 minutes and then allowed to stand 2 hours. Two ml. of isopropanol is added. After 3 hours, ether is added and organic layer separated. The organic layer is washed with aqueous sodium bicarbonate and brine, dried over calcium sulfate and concentrated under reduced pressure to yield isopropyl ll-methoxy- 3,7,11-trimethyldodeca-2,4-dienoate (about 91% trans, trans) which can be purified by chromatography and dis tillation.

Using the foregoing procedure, each of 3-thiacyclohexanol, 2,2,2-trifluoroethanol, t-butanol, 2-methoxyethanol, Z-methylthioethanol and s-butanol provides 3'-thiacyclohexyl 11-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienoate,

2,2,2'-trifluoroethyl 1 1-methoxy-3,7,1 l-trimethyldodeca-2,4-dienoate,

11 3' t-butyl 1 1-methoxy-3,7,1 1-trimethyldodeca-2,4-dienoate, 2'-methoxyethyl 11-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienoate, 2'-methylthioethyl ll-methoxy 3,7,1 l-trimethyldodeca- 2,4-dienoate, and s-butyl 11-methoxy-3,7,1 1-trimethyldodeca-2,4-dienoate.

Each of the esters of primarily the trans(2), trans(4) isomer.

EXAMPLE 36 Sodium ethoxide (prepared from 0.2 g. of sodium and 12 ml. of ethanol) is slowly added to a mixture of 1.1 g. of 7-ethoxy-3,7-dirnethyloctan-l-al, diethyl 3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate and 50 ml. of dimethylformamide, with stirring, under nitrogen, at The reaction is stirred for 1.5 hours after addition is complete and then worked up by extraction with ether to yield ethyl 11-ethoxy-3,7,11-trimethyldodeca-2,4-dienoate, mostly trans(2), trans(4), which can be further purified by chromatography and distillation.

EXAMPLE 37 To a mixture of 10 g. of 7-methoxy-3,7-dimethyloctanl-al, 17 g. of diethyl 3-ethoxycarbonyl-2-methylprop-2- enyl phosphonate (77% trans), and 150 ml. of dimethylformamide, under nitrogen, 0, with stirring, is added sodium isopropanolate (prepared from 1.5 g. of sodium in 150 ml. of isopropanol). After addition is complete, the reaction is stirred for 18 hours at room temperature and then worked up by extraction with hexane to yield isopropyl l1 methoxy-3,7,l1-trimethyldodeca-2,4-dienoate (mostly trans-2, trans-4), which can be chromatographed and distilled for further purification.

EXAMPLE 38 A mixture of g. of hydroxycitronellal (7-hydroxy-3,7- dimethyloctan-l-al), 8.5 g. of di-isopropyl 3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate, and 40 ml. of dimethylformamide, under nitrogen and cooled in an icebath, is stirred for 0.5 hour and then ground NaOH (1.165 g.) is added. The reaction mixture is stirred at room temperature for three hours and then hexane/ water (1/ 1) added. The organic layer is washed with water and brine, dried over calcium sulfate and concentrated. The concentrate is filtered through Florisil using hexane and hexane/ether. The filtrate is concentrated and then distilled to yield ethyl 1l-hydroxy-3,7,1l-trimethyldodeca- 2,4-dienoate (about 85% trans-2, trans-4).

The process of this example is repeated with the exception of using di-isopropyl 3-isopropoxycarbonyl-Z-methylprop-Z-enyl phosphonate to prepare isopropyl ll-hydroxy- 3,7,11-trimethyldodeca-2,4-dienoate, about 78% trans(2), trans(4) and 21% cis(2),trans(4).

EXAMPLE 39 To 40 ml. of ice cold isopropanol is added 2.49 g. of acetyl chloride. The resulting solution is stirred at 0 for 15 min. and 1.0 g. of trans isopropyl 3,7,l1-trimethyldodeca 2,4,10-trienoate added. The solution is stirred for one hour at 0 and for 48 hours at 25. Solvent is removed under reduced pressure and the concentrate taken up in hexane. The hexane solution is washed with water until the aqueous wash is neutral and then with brine. The solution is dried over calcium sulfate and solvent evaporated to yield trans isopropyl 11-chloro-3,7,1l-trimethyldodeca-2,4-dienoate.

EXAMPLE 40 (A) 100 Grams of 3,7-dimethyloct-6-en-1-ol is dissolved in 150 ml. of pyridine and 100 ml. of acetic anhydride and left at room temperature for about 48 hours. Then the mixture is extracted with ether and the ethereal extracts washed with water, aqueous HCl and brine to 14 yield 1-acetoxy-3,7-dimethyloct-6-ene which is purified by distillation.

(B) 150 Grams of mercuric acetate in 400 ml. of dry ethanol is added to g. of 1-acetoxy-3,7-dimethyloct-6- ene (citronellol acetate) in 200 ml. of dry ethanol cooled in an ice bath. The temperature is allowed to come to room temperature by standing overnight. Then the mixture is cooled to 0, 100 g. of potassium hydroxide in 1.5 l. of ethanol is added followed by addition of 10 g. of sodium borohydride in small portions. After about 30 minutes at 0, water (100 ml.) is added and mixture left at room temperature for two hours. The mixture is filtered, filtrate concentrated and extracted with ether. The ethereal extract is washed, dried and evaporated to yield 7-ethoxy-3,7-dimethyloctan-1-ol which is purified by distillation or chromatography.

By using methanol in the foregoing process in place of ethanol, there is obtained 7-methoxy-3,7-dimethyloctan-1- 01.

(C) A mixture of 1.9 of 7-ethoxy-3,7-dimethyloctan-1- 01 and 10 ml. of pyridine is added to a suspension of 8.0 g. of chromium trioxide in 100 ml. of pyridine with stirring under nitrogen. After about 4 hours at room temperature, the reaction is poured into saturated sodium bicarbonate and worked up with ether followed by washing with 2N NaOH, water, 10% HCl, water and brine and evaporated under reduced pressure to dryness and then filtered with hexane to yield 7-ethoxy-3,7-dimethyloctau- 1-al.

(D) A mixture of 9.0 g. of 7-ethoxy-3,7-dimethyloctanl-al and 15 g. of triphenylphosphineacetylmethylene in 100 ml. of dry toluene, under nitrogen, is refluxed for 20 hours. Thereafter, the toluene is evaporated and pentane added to remove triphenylphosphine. After concentration, the product is distilled to yield 10-ethoxy-6,10-dimethylundec-3-en-2-one. The thus-prepared ketone is reacted with the carbanion of diethyl carbethoxymethylphospho-} nate using the procedure of Example 1 or 9 to prepare ethyl- 1 l-ethoxy-3,7,l 1-trimethyldodeca-2,4-dienoate.

EXAMPLE 41 Each of the aldehydes under col. XIV is reacted with the carbanion of di-isopropyl 3-isopropoxycarbonyl-2- methylprop-Z-enyl phosphonate using the procedure of Example 38 to prepare the respective isopropyl ester under col. XV.

XIV

3 ,6,7-trimethyloct-6-enl-al 3 ,6,7-trimethylnon-6-enl-al 2,5-dimethylhex-4-en-l-al 2,4,5 -trimethyl-4-enl-al 3,5 ,6-trimethylhept-5-en-l-al 2,5 ,6-trimethylhept-5-en-l-al 3 ,8-dimethylnon-7-en-1-al 3 ,9-dimethyldec-8-enl-al.

isopropyl isopropyl isopropyl isopropyl isopropyl isopropyl isopropyl isopropyl The reaction of the aldehydes under col. XIV with the carbanion of diethyl 3-meth0xycarbonyl-2-rnethylprop-2- enylphosphonate yields the respective methyl tri-unsaturated esters. In the same way the respective ethyl tri-unsaturated esters are prepared using diethyl 3-ethoxy-carbonyl-Z-methylprop-2-enylphosphonate.

Hydrochlorinated derivatives of the above esters are prepared using the procedure of Example 14 or 39. For example,

isopropyl 11-chloro-3,7,10,1l-tetramethyldodeca- 2,4-dienoate,

isopropyl l 1-chloro-3,7,10,ll-tetrarnethyltrideca- 2,4-dienoate,

isopropyl 10-chloro-3,7,9,10-tetramethylundeca- 2,4-dienoate, and

insopropyl 12-chloro-3,7,IZ-trimethyltrideca- 2,4-dienoate.

Following the procedure of Example 23 or 29, methanol is added to the terminal double bond of each of the esters under col. XV to prepare:

In the same way, ethanol is added to the terminal double bond to prepare the respective ethoxy substituted 2,4- dienoates. Using the procedure of Example 20, water is added to the terminal double bond to prepare the respective hydroxy-substituted 2,4-dienoate.

EXAMPLE 42 (A) Eighty ml. of a 3M solution of methylmagnesiurn bromide in ether is added slowly to 31 g. of citronellal in 250 ml. of dry ether. The mixture is heated at reflux for about one hour, cooled to 0 and treated with saturated aqueous ammonium chloride until reaction subsldes. The organic layer is separated and the aqueous layer extracted with ether. The organic layer and ether extracts are combined, Washed with water and brine and dried over magnesium sulfate. Evaporation of the solvent gives 4,8-dimethylnon-7-en-2-ol.

(B) A solution of 47 g. of 4,8-dimethylnon-7-en-2-ol in 250 ml. of methylene chloride is cooled to about 10 as a solution of 46.4 g. of sodium dichromate in 125 ml. of water is added. The mixture is maintained at about 10 as a solution of 46.3 g. of sulfuric acid in 100 ml. of water is added over about minutes. The mixture is allowed to attain room temperature and, after about 3 hours, the organic layer is separated and the aqueous layer is extracted with methylene chloride. The combined organic materials are washed with saturated potassium bicarbonate, water and saturated sodium chloride, dried over magnesium sulfate and evaporated to yield 4,8-dimethylnon-7-en-2-one.

The Grignard reaction of part A is repeated using each 3,7-dimethylnon-6-en-l-al, 3-methyl 7-ethylnon-6-en-1-al, 3,6,7-trimethyloct-6-en-1-al, 3,7,8-trimethylnon-7-en-l-al, 2,4,5-trirnethylhex-4-en-l-al, 2,5-dimethylhex 4 en-l-al, 3,5,6-trimethylhept-5-en-1-al, 3,6-dimethylhept-5-en-l-al, 2,6-dimethylhept-5-en-l-al and 2,5,6-trimethylhept-5-en-1- al in place of eitronellal to yield the respective secondary alcohol 4,8-dimethyldec-7-en-2-ol 4-methyl-8-ethyldec-7-en-2-ol 4,7,8trimethylnon-7-en-2-ol 4,8,9-trimethyldec-8-en-2-ol 3 ,5 ,6-trimethylhept-5 -en-2-ol 3,6-dimethylhept-5-en-2-ol 1 6 4,6,7-trimethyloct-6-en-2-ol 4,7-dimethyloct-6-en-2-ol 3 ,7-dimethyloct-6-en-2-ol 3,6,7-trirnethyloct-6-en-2-ol.

Each of the above alcohols is oxidized to prepare thr respective ketone 4,8-dimethyldec-7-en-2-one 4-methyl-8-ethyldec-7-en-2-one 4,7,8-trimethylnon-7-en-2-one 4,8,9-trimethyldec-8-en-2-one 3 ,5 ,6-trimethylhept-5 -en-2-one 3 ,6-dimethylhept-S-en-Z-one 4,6,7-trimethyloct-6-en-2-one 4,7-dimethyloct-6-en-2-one 3 ,7 -dimethyloct-6-en-2-one 3 ,6,7-trimethyloct-6-en-2-one.

(C) Each of the ketones of part B is reacted with the carbanion of diethyl 3-ethoxycarbonyl-2-methylprop-2- enyl phosphonate according to procedures described above to prepare the respective tri-unsaturated ester i.e.

ethyl 3,5 ,7 ,1 1-tetramethyldodeca-2,4,IO-trienoate ethyl 3 ,5 ,7,1 1-tetramethyltrideca-2,4, 1 O-trienoate ethyl 3 ,5 ,7-trime thyl-l l-ethyltrideca-2,4-trienoate ethyl 3 ,5 ,7,10,1 1-pentamethyldodeca-2,4, 1 O-trienoate ethyl 3,5 ,7, l 1,1Z-pentamethyltrideca-2,4,1 l-trienoate ethyl 3,5,6,8,9-pentamethyldeca-2,4,8-trienoate ethyl 3,5,6,9-tetramethyldeca-2,4,8-trienoate ethyl 3,5,7,9,l0-pentamethylundeca-2,4,9-trienoate ethyl 3,5,7,lO-tetramethylundeca-2,4,9-trienoate ethyl 3,5,6,lO-tetramethylundeca-2,4,9-trienoate ethyl 3,5,6,9,10-pentamethylundeca-Z,4,9-trienoate.

EXAMPLE 43 (A) Each of the ketones of part B of Example 42 is reacted with the carbanion of diethyl 3-ethoxycarbonyl- 1,2-dimethylprop-Z-enylphosphonate to prepare the respective trienoate, i.e.

ethyl ethyl ethyl ethyl ethyl 3 ethyl 3 ethyl 3 ethyl 3 (B) Each of the aldehydes under col. I is reacted with the carbanion of diethyl 3-ethoxycarbonyl-1,2-dimethylprop-Z-enyl phosphonate to prepare the respective trienoate, i.e.

7,10-pentamethylundeca-2,4,9-trienoate 5 ,6, 1 0-pentamethylundeca-2,4,9-trienoate ,4,5,6,9,10-hexamethylundeca-2,4,9-trienoate.

ethyl 3,4,7,11-tetramethyltrideca-2,4,lO-trienoate ethyl 3,4,11-trimethyl-7-ethyltrideca-2,4,IO-trienoate ethyl 3,4-dimethyl-7,l 1-diethyltrideca-2,4, 1 O-trienoate ethyl 3,4,8,12-tetramethyltrideca2,4, 1 l-trienoate ethyl 3 ,4,7, l0-tetramethylundeca-2,4,9-trienoate ethyl 3,4,7,10-tetramethyldodeca-2,4,9-trienoate ethyl 3,4,6,10-tetramethylundeca-2,4,9-trienoate.

By use of the procedure of part B of this example, other aldehydes of formula I (R is hydrogen are converted into the respective ester of formula B wherein R is hydrogen and R is methyl or other lower alkyl. Similarly following the procedure of part A of this example, other ketones of formula I (R is lower alkyl) are converted into esters of formula B wherein each of R and R is lower alkyl. Using the process of part C of Example 42 other esters of the present invention of formula B wherein R is hydrogen and R is methyl or other lower alkyl can be prepared using a ketone of formula I (R is lower alkyl) as the precursor.

1 7 (C) Each of the esters of this example and Example 42 can be hydrolyzed to the free acid according to the procedure of Example 3 or 33. The acid or acid chloride can be reacted with an alcohol such as isopropanol, t-butanol, benzyl alcohol, and the like to prepare the other esters of the present invention.

EXAMPLE 44 cyclohexyl 1 1-methoxy-3,7,1l-trimethyldodeca- 2,4-dienoate n-propyl 1 1-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienoate i-butyl 1 l-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienoate benzyl 1 1-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienoate phenyl 11-methoxy-3,7, l l-trimethyldodeca- 2,4-dienoate n-hexyl 1 1-meth0xy-3,7,1 l-trimethyldodeca- 2,4-dienoate 3',3'-dimethylpentyl l 1-methoxy-3 ,7,11-trimethyldodeca- 2,4-dienoate 2'-methylpentyl 1 1-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienoate hexan-2-y1 1 1-methoxy-3,7,1l-trimethyldodeca- 2,4-dienoate 3 '-rnethylpentyl 1 l-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienoate p-ethylphenyl l l-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienoate p-phenylethyl 1 l-methoxy-3 ,7, 1 l-trimethyldodeca- 2,4-dienoate -fluoroethyl 1 1-methoxy-3,7, l l-trimethyldodeca- 2,4-dienoate 2',2'-dichloroethyl 1 1-methoxy-3,7 ,1 l-trimethyldodeca- 2,4-dienoate 2-chloropropyl 1 1-methoxy-3 ,7,11-trimethyldodeca- 2,4-dienoate 2',2',2-trichloroethyl 1 1-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienoate p-methylthiophenyl l l-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienoate EXAMPLE 45 To a solution of 0.5 g. of trans, trans ll-methoxy- 3,7,11-trimethyldodeca-2,4-dienoic acid in 15 ml. of henzene is added, with stirring, an equivalent amount of potassium hydride. The mixture is stirred at room temperature for about 2 hours and then evaporated to give potassium 1l-methoxy-3,7,l 1-trimethyldodcca-2,4-dienoate.

In place of KH, there can be used KOH, NaOH, and the like to form the corresponding salt.

EXAMPLE 46 Methanol is added to the terminal 'bond of ethyl 3,4,7,1l-tetramethyldodeca-2,4,10-trienoate using the process of Example 23 or 29 to give ethyl 11-methoxy-3,4,7,11- tetramethyldodeca-2,4-dienoate. In the same manner, water is added to give ethyl 11-hydroxy-3,4,7,1l-tetramethyldodeca-2,4-dienoate. Similarly, there is prepared ethyl 1 1-methoxy-3,5 ,7 ,1 1-tetramethyldodeca-2,4-dienoate and ethyl 11-hydroxy-3,5,7,ll-tetramethyldodeca-2,4-dienoate from ethyl 3,5,7,11-tetramethyldodeca-2,4,10-trienoate. The hydrochloride, ethyl 11-chloro-3,4,7,11- tetramethyldodeca-2,4-dienoate and ethyl 11-ch1oro-3,5,7,

11-tetramethyldodeca-2,4-dienoate are prepared from the trienoate using the process of Example 39.

EXAMPLE 47 (A) To a solution of 1.8 g. of 6,10-dimethylundeca- 3,9-dien-2-one in 20 ml. of ethanol, cooled to 0 by an ice bath is added a suspension of 2.32 g. of mercuric acetate in 50 ml. of ethanol over 15 minutes. The reaction mixture is stirred for two hours and then, with cooling, to 20, 1.22 g. of potassium hydroxide in 20 ml. of

ethanol is added. Then 0.139 g. of sodium borohydride is I added in small portions and stirring continued for 30 minutes at 20. The solution is decanted, then concentrated to half volume, diluted with ml. of water and extracted with ether (3X50). The ethereal phase is washed with water, dried over magnesium sulfate and the crude product chromatographed on silica to yield 10-ethoxy-6,10- dimethylundec-3-en-2-one.

The process of this example is repeated using each of the compounds under column VI as the starting material to prepare the respective ethoxy substituted compound under column XVI.

XVI

10-ethoxy-6, 10-dimethyldodec-3 -en-2-one 10-ethoxy-6-methyl-l0-ethyldodec-3-en-2-one 10-ethoxy-6,l0-diethyldodec-3-en-2-one 1 1-ethoxy-7,1 1-dimethyldodec-3 -en-2-one 9-ethoxy-6,9-dimethyldec-3-en-2-one 9-ethoxy-6,9-dimethylundec-3-en-2-one 9-ethoxy-5,9-dimethyldec-3-en-2-one.

Following the process of Example 13, l0-ethoxy-6,l0- dimethylundec-3-en-2-one is converted into methyl l1- ethoxy-3,7,1l-trimethyldodeca-2,4-dienoate. Reaction of 10-ethoxy-6,l0-dimethylundec-3-en-2-one with the carbanion of diethyl carboethoxymethylphosphonate yields ethyl 1 1-ethoxy-3,7,l 1-trimethyldodeca-2,4-dienoate.

By using other alcohols in the process of this example in lieu of ethanol, such as methanol, etc., the respective ethers are obtained, e.g. 10-methoxy-6,10-dimethylundec- 3-en-2-one.

(B) The process of part A is repeated using the starting material 3,7-dimethyloct-6-en-l-al and each of the aldehydes under column I or the acetal thereof to prepare the respective compounds under column XVII.

XVII

7-ethoxy-3 ,7-dimethy1octan-1-al 7-ethoxy-3,7-dimethylnonan-l-al 7-ethoxy-3-ethyl-7-methylnonan-l-al 7-ethoxy-3,7 -diethylnonan-1-al 8-ethoxy-4,8-dimethylnonan-l-al 6-ethoxy-3,G-dimethylheptan-l-al 6-ethoxy-3,6-dimethyloctan-1-al 6-ethoxy-2,G-dimethylheptan-l-al Using 7-ethoxy-3,7-dimethyloctan-l-al as the starting material in the process of either Example 9, 10 or 11, there is prepared l0-ethoxy-6,10-dimethylundec-3-en-2- one.

EXAMPLE 48 To a solution of 2 g. of methyl 3,7,ll-trimethyldodeca- 2,4,10-trienoate and 20 ml. of dry ether, at 78, is added slowly about 0.4 g. of lithium aluminum hydride in dry ether. The mixture is allowed to stand about one hour after addition is complete and, then allowed to warm up to room temperature. Then 2.5 ml. of acetic acid is added. The mixture is then washed with ice water and the organic phase separated, which is dried over magnesium sulfate and evaporated to yield 3,7,11-trirncthyldodeca-2,4,10-trien-1-ol.

19 By use of the process of this example, each of the esters under Column 11 or VII is reduced to prepare the respective allylic alcohol, i.e.,

3,7,1 1-trimethyltrideca-2,4,l0-trien-1-Ol,

3,1 1-dimethyl-7-ethyltrideca-2,4, 10-trien-1-ol, 7,1 1-diethyl-3-methyltrideca-2,4,10-trien-l-ol, 3 ,8,12-trimethyltrideca-2,4,1 l-trien- 1-01,

3 ,7,10-trimethylundeca-2,4,9-trien-1-ol,

3 ,7,10-trimethyldodeca-2,4,9-trien-l-ol, 3,6,10-trimethylundeca-2,4,9-trien-l-ol.

Each of methyl 3,7,10,1l-tetramethyldodeca-2,4,10-trienoate, methyl 11-methoxy-3,7,l1-trimethyldodeca-2,4-dienoate, methyl 10methoxy-3,7,lO-trimethylundeca-2,4-dienoate, methyl 3,5,7,11-tetramethyldodeca-2,4,IO-trienoate, methyl 3 ,4,7,1 1-tetramethyldodeca-2,4,10-trienoate, methyl 3,5,7,10,11-pentamethyldodeca-2,4,10-trienoate, methyl 11-ethoxy-3,7,11-trimethy1dodeca-2,4,-dienoate and methyl 1 1-chloro-3,7,11-trimethyldodeca-2,4-dienoate is reduced using lithium aluminum hydride to the re spective C-l alcohol, i.e.,

3,7,10, 1 1-tetramethyldodeca-2,4,10-trien-l-ol, 11-methoxy-3 ,7,11-trimethylundeca-2,4-dien-1-ol, 10-methoxy-3,7,10-trimethylundeca-2,4-dien-1-01, 3,5 ,7, 1 1-tetramethyldodeca-2,4, IO-trien- 1-ol, 3,4,7,11-tetramethylddeca-2,4,lO-trien-l-ol,

3 ,5,7,10,1l-pentamethyldodeca-2,4,10-trien-1-ol,

1 l-ethoxy-3,7 ,1 1-trimethyldodeca-2,4-dien-l-ol and 11-chloro-3 ,7,11-trimethyldodeca-2,4-dien-1-ol.

EXAMPLE 49 To a mixture of 4 g. of 3,7,11-trimethyldodeca-2,4,10- trien-l-ol and 25 ml. of benzene at 0 is added a solution of 5 ml. of phosphorus tribromide in 18 ml. of benzene over about minutes. The mixture is stirred at 0 for one hour. The mixture is then poured onto ice and extracted with pentane. The organic phase is washed with aqueous sodium bicarbonate, water and then brine, dried over magnesium sulfate and evaporated to yield l-bromo- 3,7,11-trimethyldodeca-2,4,IO-triene.

The process of this example is repeated using each of the alcohols of Example 48 to prepare the respective bromide, i.e.,

3,7,1 l-trimethyltrideca-2,4,10-trienyl bromide,

3,1 1-dimethyl-7-ethyltrideca-2,4, lO-trienyl bromide,

7,1 1-diethyl-3-methyltrideca-2,4, lO-trienyl bromide, 3,8,12-trimethyltrideca-2,4,1 l-trienyl bromide, 3,7,10-trimethylundeca-2,4,9-trienyl bromide, 3,7,10-trimethyldodeca-2,4,9-trienyl bromide, 3,6,10-trimethylundeca-2,4,9-trienyl bromide,

3,7, 10,1 1-tetramethyldodeca-2,4, 1 O-trienyl bromide,

1 1-methoxy-3,7,11-trimethyldodeca-2,4-dienyl bromide, 10-methoxy-3,7,10-trimethylundeca-2,4-dienyl bromide, 3,5,7,1l-tetramethyldodeca-2,4,IO-trienyl bromide 3,4,7,1 1-tetramethyldodeca-2,4, 1 O-trienyl bromide,

3,5 ,7, 1 0, 1 l-pentamethyldodeca-2,4, 1 O-trienyl bromide,

1 1-ethoxy-3,7,11-trimethyldodeca-2,4-dienyl bromide, 11-chloro-3,7,11-trimethyldodeca-2,4-dienyl bromide.

By repeating the process of this example using phosphorus trichloride in place of phosphorus tribromide, the novel allylic chlorides are prepared, i.e., 3,7,11-trimethyldodeca-2,4,10 trienyl chloride, 3,7,11-trimethyltrideca-2,4,10-trienyl chloride, 3,11 dimethyl-7-ethyltrideca-2,4,10-trieny1 chloride, etc.

EXAMPLE 50 Ten grams of 1-bromo-3,7,11-trimethyldodeca-2,4,10- triene is mixed with 50 ml. of benzene, cooled to 5-10 and saturated with ammonia. The resulting mixture is stirred for four hours allowing the temperature to rise to about while maintaining dry conditions. The mixture is washed with dilute sodium hydroxide and then evaporated under reduced pressure to yield 3,7,11-trimethyldodeca-2,4,10-trienylamine.

By repeating the process of this example using the allylic bromides or chlorides of Example 49, the respective amines are prepared, e.g., 3,7,11-trimethyltrideca-2,4,l0- trienylamine, 3,11-dimethyl 7 ethyltrideca-2,4,10-trienylamine, 1 l-methoxy-3,7,11-trimethyldodeca-2,4-dienylamine, 10 methoxy-3,7,10-trimethylundeca-2,4-dienylamine, 11chloro-3,7,l1-trimethyldodeca 2,4 dienylamine, etc.

EXAMPLE 51 Five grams of 1-bromo-3,7,11-trimelhyldodeca-2,4,10- triene in 25 m1, of benzene is mixed with 4 g. of diethylamine and the mixture stirred for about three hours. Methylene chloride (50 ml.) is added and the mixture washed with dilute sodium hydroxide and then water and evaporated to yield N,N-diethyl 3,7,11-trimethyldodeca- 2,4,10-trienylamine.

The process of this example is repeated using either the bromides or chlorides of Example 49 as the starting material to prepare the respective N,N-diethyl amine, e.g.,

N,N-diethyl 3,7,1 1-trimethyltrideca-2,4, 1 O-trienylamine,

N,N-diethyl 3,1 1-dimethyl-7-ethyltrideca-2,4,10-

trienylamine,

N,N-diethyl 1 1-methoxy-3 ,7,1 1-trimethyldodeca-2,4-

dienylamine,

N,N-diethyl 10-methoxy-3,7,10-trimethylundeca-2,4-

dienylamine,

N ,N-diethyl 1 1-chloro-3,7,11-trimethyld0deca-2,4-

dienylamine,

N,N-diethyl 3,7,10-trimethylundeca-2,4-dienyl amine, etc.

Other amines of the present invention of formula A and B are prepared by use of the foregoing procedure using an amine of the formula:

such as dimethylamine, ethylamine, methylamine, pyrrolidine, morpholine, 4-ethylpiperazine, and the like, in place of diethylamine. Thus, there is prepared N,N-dimethyl 3,7,11 trimethyldodeca-2,4,10-trienylamine, N,N- dimethyl 3,7,11 trimethyltrideca-2,4,IO-trienylamine, N- ethyl 3,7,11-trimethyldodeca2,4,IO-trienylamine, N-ethyl- 3,7,11-trimethyltrideca-2,4,IO-trienylamine, etc.

EXAMPLE 52 By use of the process of Example 20, water is added to the terminal double bond of the tri-unsaturated amines of formula B to produce the respective hydroxy derivatives, e.g.,

N,N-diethyl 11 hydroxy-3,7,11-trimethyldodeca-2,4- dienylamine,

N,N-diethyl 11 hydroxy-3,7,11-trimethyltrideca-2,4- dienylamine,

N,N dimethyl l1 hydroxy-3,7,1l-trimethyldodeca- 2,4-dienylamine,

N ethyl l1 hydroxy-3,7,11-trimethyldodeca-2,4-dienylamine, and

N-methyl ll-hydroxy 3,7,11 trimethyldodeca 2,4- dienylamine.

The thus-prepared free hydroxy compounds can be esterified' using the procedure of, e.g., Example 24 and 25, to form the respective esters, e.g., the respective 11- acetate.

Although not intending to be limited by a theoretical explanation, the effectiveness of the compounds of the present invention to control insects is attributed to the property of these novel compounds to mimic the activity of juvenile hormone. While the methods of applying and carriers for conventional insecticides are usually adaptable to the practical use of the compounds of the present invention, the mechanism of action of these novel compounds is unlike that of conventional insecticides. Whereas conventional insecticides are dependent upon direct knock-down effect, toxity effect or paralyzing effect, the compounds of this invention achieve control by reason of their ability to inhibit metamorphosis, inhibit reproduction due to abnormal development, break diapause at an unfavorable time, or act as a direct insecticide, particularly at the embryo stage and larvae stage. Treatment of insects in accordance with the present invention can be achieved via ingestion of the active compound in the normal food of the insect and by topical application, that is-by contact of the epidermis of the insect as by spraying the insect and habitat of the insect or exposure to vapors of the active compound which penetrate into the insect.

The compounds of the present invention can be used in conjunction with other juvenile hormone active substances and conventional insecticides to obtain a broad spectrum of activity or to provide more immediate effect on very heterogeneous populations. Typical insecticides which may be combined with the compounds of the present invention are: Malathion, Sevin, Vapona, Abate, synthetic and natural pyrethrins, and the like, and usually within the ratio of between :1 to 1:10, by weight.

EXAMPLE 54 To a solution of 6.2 g. of ethyl 11-methoxy-3,7,ll-trimethyldodeca-Z,4-dienoate in 80 ml. of dry ether is added 3.2 ml. of lithium aluminum hydride (3.9M) in ether slowly, at 78", with stirring, under argon. The mixture is stirred for two hours at 78 and then warmed to about 50. After one hour, the mixture is warmed slowly to about -10 over four hours. Then there is added 0.5 ml. of water, 0.5 ml. of 15% sodium hydroxide and 1.5 ml. of water. The mixture is then poured into water, washed with water and brine, dried over magnesium sulfate and evaporated to yield 11-methoxy-3,7,11-trimethyldodeca-2,4-dien-l-ol.

EXAMPLE 55 To a solution of 1.90 g. of 1l-methoxy-3,7,1l-trimethyldodeca-2,4-dien-l-ol in ml. of ether is added a solu- 22 tion of 0.80 g. of phosphorus tribromide in 10 ml. of ether, under nitrogen, with stirring at 50. The reaction mixture is stirred for three hours at 60 to 40 and then poured into ice water, which is then Washed with sodium bicarbonate solution, water and brine, dried over calcium sulfate and evaporated under reduced pressure to yield 11 methoxy 3,7,11 trimethyldodeca-2,4-dienyl bromide.

EXAMPLE 56 To a solution of 2g. of 3,4-methylenedioxyaniline and 10 ml. of dimethylformamide is added 4.5 g. of ll-methoxy-3,7,lltrimethyldodeca-2,4-dienyl bromide and 2.5 g. of potassium carbonate. The reaction mixture is heated at about 60 for about eight hours. After cooling, the mixture is diluted with water and extracted with ether. The ethereal layer is dried over calcium sulfate and evaporated to yield -N-1l-methoxy-3,7,1l-trimethyldodeca-2,4- dienyl 3,4-methylenedioxyaniline, which can be purified by chromatography.

EXAMPLE 57 A suspension of 0.5 g. of sodium hydride in mineral oil is stirred, under nitrogen, with 15 ml. of dioxane and then 1.5 g. of p-ethylphenyl amine in 10 ml. of dioxane is added. The mixture is stirred and then 3.0 g. of 11-methoxy-3,7,11-trimethyldodeca-2,4-dienyl bromide in 15 ml. of dioxane is added and the mixture refluxed for about two hours. After cooling, the mixture is filtered and the filtrate evaporated under reduced pressure. The residue is mixed with water and ether and the ether phase separated. The ether and the ether phase is washed with dilute HCl, dried over calcium sulfate and evaporated to yield N-ll-methoxy-3,7,ll-trimethyldodeca-2,4- dienyl p-ethylphenyl amine, which can be purified by chromatography.

EXAMPLE 58 Using the procedure of Example 14, each of N,N-diethyl-3,7,11-trimethy1dodeca-2,4,IO-trienyl amine, N,N- dimethyl 3,7,1l-trimethyldodeca-2,4,IO-trienyl amine, N- methyl-N ethyl 3,7,l1-trimethyldodeca 2,4,l0-trieny1 amine, N-ethyl 3,7,11-trimethyldodeca 2,4,l0-trieny1 amine and N-isopropyl 3,7,1l-trimethyldodeca-2,4,IO-trienyl amine is hydrochlorinated to yield the respective 11- chloro derivative.

N,N-diethyl ll-chloro 3,7,1l-trimethyldodeca-2,4-dienyl amine,

N,N-dimethyl 1l-chloro-3,7,11 trimethyldodeca-2,4- dienyl amine,

N-methyl-N-ethyl ll-chloro-3,7,l1 trimethyldodeca- 2,4-dienyl amine,

N-ethyl 11-chloro-3,7,1l trimethyldodeca-2,4-dienyl amine and N-isopropyl 11-chloro-3,7,11 trirnethyldodeca-2,4-dienyl amine.

What is claimed is:

1. A compound selected from those of the formula (A):

wherein Z is bromo, chloro, fluoro, or the group OR in which R is hydrogen, acetoxy, or lower alkyl;

Z is hydrogen, bromo, chloro or fluoro;

n is zero or the positive integer one;

each of R R R and R is lower alkyl;

each of R R and R is hydrogen or lower alkyl; and

each of R and R is hydrogen, lower alkyl, or lower alkenyl.

2. A compound according to formula A of Claim 1 wherein each of R R and R is methyl or ethyl; each of R R and R is hydrogen or methyl; Z is chloro or the group OR; and Z' is hydrogen.

3. A compound according to Claim 2 wherein R is methyl or ethyl; and each of R and R is hydrogen.

4. A compound according to Claim 3 wherein n is one; R is hydrogen; and each of R R and R is methyl.

5. A compound according to Claim 4 wherein each of R and R is hydrogen or lower alkyl.

6'. A compound according to Claim 5 wherein Z is methoxy or ethoxy.

7. A compound according to Claim 6 wherein each of R and R is hydrogen, methyl, ethyl or isopropyl.

8. A compound according to Claim 3 wherein n is one; R is methyl; and each of R and R is hydrogen or lower alkyl.

9. A compound according to Claim 8 wherein Z is chloro or the group OR in which R is hydrogen or lower alkyl of one to four carbon atoms.

10. A compound according to Claim 9 wherein each of R R R and R is methyl and each of R and R is hydrogen or lower alkyl of one to four carbon atoms.

11. A compound according to Claim 10 wherein Z is chloro and R is hydrogen.

12. A compound according to Claim 10 wherein Z is methoxy and R is hydrogen.

13. A compound according to Claim 10 wherein Z is hydroxy and R is hydrogen.

14. A compound according to Claim 11 wherein each of R and R is hydrogen, methyl, ethyl or isopropyl.

15. A compound according to Claim 14 wherein R is methyl, ethyl or isopropyl and R is hydrogen.

16. A compound according to Claim 12 wherein each of R and R is hydrogen, methyl, ethyl or isopropyl.

17. A compound according to Claim 16 wherein R is methyl, ethyl or isopropyl and R is hydrogen.

18. A compound according to Claim 13 wherein each of R and R is hydrogen, methyl, ethyl or isopropyl.

19. A compound according to Claim 18 wherein R is methyl, ethyl or isopropyl and R is hydrogen.

References Cited UNITED STATES PATENTS 3,671,558 6/1972 Siddall et a1 260--583 H 3,692,851 9/1972 Henrick et a1. 260-583 H 2,951,853 9/1960 Matsui 260-583 H 3,429,970 2/1969 Ruegg et a1. 260583 H 3,541,154 11/1970 Schmialek et a1. 260583 H OTHER REFERENCES Nature, vol. 223, July 19, 1969, pp. 316-317.

ELBERT L. ROBERTS, Primary Examiner D. R. PHILLIPS, Assistant Examiner 

1. A COMPOUND SELECTED FROM THOSE OF THE FORMULA (A): 